Purpose

To investigate diagnostic performance of amide proton transfer–weighted (APTw) magnetic resonance imaging (MRI) biometrics for differentiation of low-(LGG) and high-grade glioma (HGG) in patients.

Introduction

Malignant brain tumors have an incidence of 29.5 / 100 000 individuals yearly.¹ Primary brain tumors have an overall five-year survival rate of only 33.4 % with prognostic factors being better in the gliomas of lower grades (I-II) in comparison with those of higher grades (III-IV).² Multidisciplinary team efforts are of importance for individualized treatment as options include surgery, radiotherapy, chemotherapy, or a combination of these.² Conventional Gadolinium-based T1w and T2w MRI techniques are the standard for diagnosing and preoperatively evaluating patients with brain tumors.² The main problem is that grade II oligodendrogliomas and low-grade astrocytomas do occasionally enhance while up to 33 % of HGG do not enhance, which may cause delays in diagnosis and/or treatment with consequent worsening of prognosis.³ APTw is based on that exchangeable amide protons in proteins can be detected with MRI by using a method called chemical exchange saturation transfer (CEST) MRI.⁴ APTw imaging provides spatial information regarding proteins peptides and may yield improved diagnostics regarding, e.g. tumor grade and earlier detection of brain tumors.^5,6 Therefore, APTw imaging has the potential to provide further individualised treatment options through faster and more accurate diagnosis of primary brain tumors of de novo origin.

Method

Twenty patients (2 females and 18 males) were recruited. The mean age at diagnosis of patients with HGG (n=13) was 54 years (range: 30–73 years) and of patients with LGG (n=7) was 52 years (range: 46–62 years). All subjects had biopsy-verified tumors graded according to the World Health Organisation (WHO) classification ( Table 1). The patients were examined on a 3T scanner (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany). APTw images were generated using a CEST prototype sequence based on a 3D GRE (22 slices, 2x2x4 mm3) acquisition of a water saturation spectrum (Z-spectrum, 21 offset points from -610 to 610 Hz, B1=2 µT, tsat = 600ms, 5 hyperbolic secant pulses, 60 ms interpulse delay, TA 6:50min), followed by B0 correction and processing optimized for APTw contrast at 3.5 ppm. Image analysis was performed in RadiAant DICOM Viewer (Medixant, Poznan, Poland). APTw data was assessed for mean and maximal value in the tumor by manually placing a region of interest (ROI), 10 pixels in diameter, within the lesion on color-converted APTw maps with support from T1-MPRAGE and FLAIR images. Mann-Whitney U tests and subsequent ROC analysis were performed in SPSS (IBM, Armonk, New York, USA).

Results and Discussion

Table 2 summarizes the patient-specific details and APTw values. Across HGG and LGG patients, the mean APTw with a cut-off value of 1.92% showed a sensitivity of 84.6% and a specificity of 57.1% (p-value <0.043) with HGG having higher mean APTw than LGG; 2.69% vs 1.63%, respectively. Figure 1. depicts the Receiver Operating Characteristic (ROC) analysis for mean APTw MRI for distinguishing HGG and LGG. The maximum APTw was also found to be higher in HGG compared to LGG 3.29% and 2.22%, respectively (p-value <0.062), although not statistically significant. Findings of higher mean APTw values in HGG indicate that increasing tumor grade corresponds to higher amount of CEST-detectable protein accumulation (Table 2). Patients 11, 14 and 16 in the LGG group exhibited somewhat surprisingly higher mean APTw than the others (Table 2). Patients; 9, 12 , 17, with lower mean APTw signal were predominantly IDH-1 mutants with patient 3 being IDH-wildtype (Table 2). This may suggest that different APTw intensities may correlate to different mutations as previously shown.⁷ Patient 12 near-normal APT-values suggest impact of oligoastrocytomas having mixed areas of oligodendroglial and astrocytic cells and mutations (Table 2).⁸ This study resulted in comparable degrees of sensitivity (Figure 1) in differentiation between LGG grade II and glioblastoma grade IV but with lower specificity (Figure 1). Implications for therapeutic planning are obvious as gliomas of different grades have varying prognosis.⁹ Main limitations are the size of the cohort and patient movement.

Conclusion

APT-weighted imaging provides differential information for HGG/LGG and shows promise as a clinically valuable tool for distinction between glial tumors of grades II and IV.

Acknowledgements

No acknowledgement found.

References

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